Hi, it depends what you mean by "production." In my previous message I took it to mean physical production in cell culture as needed for clinical trials or commercial production.
It is well known that "pure" mouse Abs (or rather the cell lines that make them) from original hybridomas tend to be a lot more "productive" in this sense than engineered, transfected Abs in host cell lines. In this interpretation I see no intrinsic "productivity" difference between primatized, CDR-grafted (this is the "original" humanization technique) or resurfaced Abs.
Now, in their press releases, I think IMGN's statement of "greater advantange in production" refers to the ease in which, theoretically, one may come up with a "humanized" construct using resurfacing vs. using CDR-grafting. As outlined before, both approaches start with the V domains of a mouse Ab (or perhaps rat or some other "lower" critter). Then one has to decide which and how many of the amino acids in those domains can be "safely" changed to human equivalents (by safely I mean that the resulting V domain will still lead to an Ab with good binding affinity). IMGN would claim that this process may be accomplished more easily with resurfacing than with other techniques. I do not necessarily agree with this, but this is what they seem to claim.
However, after that part is taken care of, one has to come up with a high-producing cell line that expresses your product. At this point, as I said before, I see no intrinsic advantage -- for production -- for any of one these processes over the others.
Note that for IMGN's apparent definition of "advantage in production" IPEC's primatized is even better as one does not have to spend any time engineering anything because the monkey has done the job for you (i.e., come up with a human-like V domain that recognizes the antigen of interest). Of course, it is easier to work with mice than with monkeys in the first place, but all this happens in the very first step of Ab production/discovery and that would be the immunization with the antigen of interest. With IPEC's approach you pay the price early by having to work with monkeys and then with monkey cells, which is not as easy as the same with mice's or rats'. But once you have the V domains (monkey's) for the Ab you want, you are done. Just "cut and paste" them with human C regions. With the humanization approaches the first step is easier because you're working with mice or rats, but then you have to spend some time redesigning the mouse V domains (resurfacing them, or "reshaping" them, or "CDR-grafting" them, or making them "SMART" -- the latter is PDL's trademark for their technology, etc). So, as in anything else in life, there is no free lunch.
Hope this makes more sense now and gave a nice afternoon too,
Max |
